Uniaxial strain regulates morphogenesis, gene expression, and tissue strength in engineered skin

Mechanical properties of engineered tissues should ideally match those of the tissues that are replaced. Engineered skin (ES) is often orders of magnitude weaker than normal skin, which can lead to damage during application and improper function after engraftment. Hypothetically, application of strain during culture of ES may lead to improved mechanical properties. ES comprised of electrospun collagen scaffolds, human dermal fibroblasts, and epidermal keratinocytes were fabricated and cultured at the air-liquid interface. ES was loaded in vitro into a strain apparatus, strained to 0% (restrained), 5%, 10%, 20%, or 40%, with unstrained ES as a control, and cultured for 10 days. ES cultured under 10% and 20% strain were significantly stronger than unstrained controls. ES cultured under 20% strain showed upregulation of many genes encoding structural extracellular matrix proteins, including collagen type I alpha 1 and fibronectin 1. Mechanical stimulation significantly increased epidermal cell proliferation and enhanced epidermal differentiation with 5%, 10%, and 20% strain. Improved strength in the 10% and 20% strain groups is likely a result of increased extracellular matrix production coupled with enhanced epidermal differentiation. These improvements to ES may facilitate surgical application, prevent damage during transplantation, and may result in improved functional outcomes after engraftment.